Periampullary and Pancreatic Tumors Rod L. Flynn, M.D. Surgical Oncologist Mary Washington Hospital Fredericksburg, VA

Periampullary Tumors Defined as those that arise within 2 cm of the major papilla in the duodenum Classified on the basis of their tissue of origin Often difficult or impossible to differentiate from pancreatic head adenocarcinoma before performing a resection

Periampullary Tumors Encompass tumors of the: ampulla of Vater distal common bile duct (intrapancreatic distal common bile duct), duodenal tumors (usually the second part) involving the papilla tumors of the pancreatic head involving in close proximity to the ampulla Pancreatic head adenocarcinoma accounts for most (approximately 80%) tumors in the periampullary region

Periampullary Anatomy

Periampullary Tumors In general, the more distal the tumor is along the pancreatobiliary tree, the better the prognosis Hilar Cholangiocarcinomas (Klatskin Tumors) 15-20% 5-year survival Distal bile duct cancers 20-30% 5-year survival Ampullary carcinomas 40-60% 5-year survival Duodenal carcinomas 60% -70% 5-year survival Pancreatic head adenocarcinoma 15-20% 5-year survival Non-pancreatic periampullary cancers tend to have a better prognosis than does pancreatic adenocarcinoma because they are often more resectable i.e. 90% of ampullary cancers vs 15-20% of pancreatic head cancers

Pancreatic Head Adenocarcinoma

Pancreatic Head Adenocarcinoma Demographics Treatment poses diagnostic and therapeutic challenge Second most common GI malignancy in U.S. (colorectal is the most common) In 2006, 33,730 new cases were diagnosed in U.S. Accounted for about 32,300 deaths Fourth leading cause of cancer-related deaths (following lung, colon, breast/prostate)

Pancreatic Head Adenocarcinoma Demographics Responsible for 5% of all cancer-related deaths Surgical resection provides the only chance for cure 80% of patients present with advanced disease not amenable to resection

Pancreatic Cancer Risk Factors Exact cause is unknown Environmental exposure Smoking (main risk factor) Risk increases with dose and exposure Other tobacco carcinogens likely involved Organic and nickel-containing solvents Chlorinated compounds High BMI Diet -- low in vegetables and fruits, high in animal fats and meat products Risk higher in obese individuals Risk higher in obese individuals Decreases with weight loss and exercise

Pancreatic Cancer Risk Factors (cont’d) Comorbid conditions Chronic pancreatitis Diabetes mellitus, type II Risk doubles with > 5-year history of diabetes mellitus, type II Genetic factors Account for 15% to 20% of cases 1 family member affected: 18 times risk 3 family members affected: 57 times risk Familial syndromes

Molecular/Genetic Defect Familial Syndromes Syndrome Molecular/Genetic Defect Hereditary pancreatitis 7q35 Hereditary nonpolyposis colorectal cancer (Lynch syndrome II) hMSH2, hMLH1 Hereditary breast and ovarian cancer BRCA2 Familial atypical multiple mole melanoma (FAMM) p16 (9p21) Peutz-Jeghers syndrome STK11/LKB1 (19p13) Ataxia-telangiectasia (ATM) syndrome 11q22-23

Pancreatic Head Adenocarcinoma Clinical Presentation Most patients with periampullary cancer present with at least one of the following symptoms: Weight loss Jaundice (75% of patients) Vague epigastric/ back pain (retroperitoneal plexus invasion) Fatigue Intestinal malabsorption New onset diabetes (15%) Symptom complex is vague, which often delays presentation and diagnosis As a result about 80% of all patients present with unresectable disease

Pancreatic Head Adenocarcinoma Clinical Signs The presence of clinical signs usually means advanced disease Courvoisier’s sign Painless jaundice Palpable abdominal mass Large tumor or omental cake Ascites Umbillical nodule (Sister Mary Joseph’s node) Blumer’s shelf (rectovaginal/vescicle mass) Virchow’s node (left supraclavicular)

Pancreatic Cancer Clinical Presentation Component Symptom Local Epigastric/back pain Constitutional Fatigue Anorexia Weight loss Biliary obstruction Jaundice Pruritus Pale stools Malabsorption of fat-soluble vitamins Pancreatic insufficiency Malabsorption

AJCC STAGING Pancreatic Cancer TUMOR Tis: in situ carcinoma T1: < 2 cm T2: > 2 cm T3: beyond pancreas T4: involves celiac axis or superior mesenteric artery (unresectable) NODE N0: no lymph node metastases N1: regional lymph node metastases METASTASES M0: no distant metastases M1: distant metastases present Stage 0 Tis, N0, M0 Stage IA T1, N0, M0 Stage IB T2, N0, M0 Stage IIA T3, N0, M0 Stage IIB T1-3, N1, M0 Stage III T4, any N, M0 Stage IV Any T, any N, M1

Pancreatic Cancer Diagnosis The goals of evaluating patients with periampullary cancers is to obtain diagnosis and clinical stage Based on these determinations the patient can be triaged into a treatment category (operative or non-operative) At time of initial diagnosis, approx 50% of patients will have metastatic disease 30% will have locally-advanced disease not amenable to surgical resection The superior mesenteric vein is involved with the large pancreatic head tumor

Pancreatic Cancer Diagnostic Tests Blood tests including CBC, LFTs, amylase/lipase, CEA, CA 19-9 Abdominal ultrasound A common initial test to evaluate jaundice Abdominal CT scan Gives better anatomical information on the source of the biliary obstruction Can give information about extrapancreatic sites of spread (liver, peritoneal/omental surfaces, ascites, extensive nodal involvement, adjacent organ involvement) Can assess involvent of major blood vessels (SMA/portal vein) Angiography ? PET scan

Pancreatic Cancer Diagnostic Tests ERCP Brush cytology Stenting if necessary Look for dilated pancreatic duct Look for filling defect within bile duct

Pancreatic Cancer Diagnostic Tests Endoscopic ultrasound Can detect very small tumors (<2cm) Can assist in staging by assessing mesenteric vascular involvement FNA biopsies are relatively easy to do Operator dependant

Laparoscopy for staging Looking for Local involvement of adjacent organs Loco-regional extension (lymph nodes, soft tissue) Small liver metastases Peritoneal nodules Peritoneal Nodule

Treatment Available Chemotherapy Radiation therapy Chemoradiation followed by resection Resection Resection + Adjuvant Therapy Palliation Stents Bypass Feeding tubes

Treatment Available Only 10-20% of patients are eligible for surgery Most have advanced disease at time of diagnosis Most common chemo 5-FU & Gemcitabine

Pancreaticoduodenectomy Whipple Procedure Pancreaticoduodenectomy The Whipple operation was first described in the 1930’s by Allan Whipple In the 1960’s and 1970’s the mortality rate for the Whipple operation was very high (Up to 25% of patients died from the surgery) This experience of the 1970’s is still remembered by some physicians who are reluctant to recommend the Whipple operation Today the Whipple operation has become an extremely safe operation in the USA - At tertiary care centers where large numbers of these procedures are performed by selected surgeons, the mortality rate is less than 4%.

Most common Diagnosis of patients undergoing Whipple Peripancreatic Cancer (jaundice) Pancreatic head Ampulla Bile duct Duodenal wall Pancreatitis Cystic neoplasm Carcinoid Islet cell tumors

Surgery Incisions Omentum Resectability (Portal Vein/SMA) Gall Bladder and Porta Hepatis Gastrectomy Pancreas Transection Reconstruction

Surgery Incisions Omentum Resectability (Portal Vein/SMA) Gall Bladder and Porta Hepatis Gastrectomy Pancreas Transection Reconstruction

Surgery (cont.) Pylorus Preserving Extended Nodal Dissection Gastric Inversion

Surgery (cont.) Exposure of SMV

Surgery (cont.) Portal Triad Hepatic artery Portal vein Common bile duct

Surgery (cont.) Division of pancreas

Surgery (cont.) Resected specimen

Surgery (cont.) Plumbing restored

Outcomes Possible complications 44% in modern series out of Johns Hopkins; <5% 30-day mortality; 17day LOS v. 28 for complicated Pancreatic fistula (Leak-8%) Gastro paresis Nutritional deficiencies Malabsorption Early satiety Weight loss Diabetes

Outcomes (Johns Hopkins study, con’t) N= 201 patients The mean age of the patients was 63 years, with a slight male predominance (108 men and 93 women). There were no differences in survival based on age, gender, or race. The actuarial one, three and five-year survival rates for all 201 patients were 57%, 26%, and 21% respectively, with a median survival of 15.5 months. 11 five-year survivors, 7 six-year survivors one fifteen-year survivor.

Summary Periampullary cancers include bile duct, ampulla of vater, duodenal, pancreatic head Prognoses depend on relative location Pancreatic head adenocarcinoma carries worst prognosis Surgery is the only chance of cure, although a majority of patients are unresectable at the time of diagnosis Better preoperative evaluation can reduce the number of unnecessary operations Preoperative diagnosis is often very difficult if not impossible to make despite a myriad of diagnostic modalities at our disposal In this group of patients we surgeons sometime have to tell the patient after a lengthy Whipple operation: “…I have good news, you don’t have cancer…”

Bye-bye